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| ID | Type | Description | Link |
|---|---|---|---|
| 54861911ALZ2002 | Other Identifier | Janssen Research & Development, LLC | |
| 2014-002159-24 | EudraCT Number |
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The purpose of this study is to evaluate the long-term safety and tolerability of JNJ-54861911 during 6 months of treatment in participants with early (predementia) alzheimer's disease (AD [degenerative disease of the brain characterized by the insidious onset of dementia, impairment of memory, judgment, attention span, and problem solving skills are followed by severe apraxias and a global loss of cognitive abilities]).
This is a double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect), randomized (study drug assigned by chance), multi-center (when more than one hospital or medical school team work on a medical research study), parallel-group study. The study consists of 3 Parts; Screening Phase of 90 days, double-blind Treatment Phase of 6 months and Follow-up Phase of 7 to 28 days following the last dose in Month 6. Eligible participants in the early (predementia) AD spectrum will be randomized to either Treatment group 1, 2 or placebo and participants who previously participated in study 54861911ALZ1005 will be enrolled in this study and will receive the same treatment as in study 54861911ALZ1005. The study duration for each participant will be approximately 10 months. Blood and cerebrospinal fluid (CSF) samples will be collected to evaluate the plasma pharmacokinetics of JNJ-54861911, as well as amyloid beta fragments. Participants' safety will be monitored throughout the study, including magnetic resonance imaging (MRI) and cognitive measures.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Group 1 | Experimental | Participants will self-administer JNJ-54861911, two tablets of 5 milligram (mg) each for a total of 10 mg, orally, once daily, from Day 1 until Month 6. |
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| Treatment Group 2 | Experimental | Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6. |
|
| Placebo | Placebo Comparator | Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JNJ-54861911, 10 milligram (mg) | Drug | Participants will self-administer JNJ-54861911, two tablets of 5 mg each for a total of 10 mg, orally, once daily, from Day 1 until Month 6 in treatment group 1. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | up to 10 months |
| Measure | Description | Time Frame |
|---|---|---|
| Relationship Between Dose and Exposure of JNJ-54861911 With Safety | Plasma and, if possible, CSF measurements will be taken to measure the concentration of JNJ-54861911. Population pharmacokinetic modeling (statistical modeling) will be used to derive individual pharmacokinetic parameters (e.g. Cmax, AUCtau, Tmax) in plasma and, if possible, in CSF. Incidence of adverse events and their timing of onset will be examined with regard to these concentrations to assess potential relationships between safety and exposure. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ghent | Belgium | |||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32410694 | Derived | Novak G, Streffer JR, Timmers M, Henley D, Brashear HR, Bogert J, Russu A, Janssens L, Tesseur I, Tritsmans L, Van Nueten L, Engelborghs S. Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer's disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study. Alzheimers Res Ther. 2020 May 14;12(1):58. doi: 10.1186/s13195-020-00614-5. |
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| JNJ-54861911, 50 mg | Drug | Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6 in treatment group 2. |
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| Placebo | Drug | Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6 in placebo group. |
|
| Month 1 up to Month 6 |
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels and Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha, sAPP-beta), Total sAPP Levels | The CSF samples will be obtained for measuring levels of different ABeta fragments such as ABeta 1-37, ABeta 1-38, ABeta 1-40, ABeta 1-42. ABeta fragments of different length are produced by cleavage of the APP by beta-secretase (BACE) and the gamma-secretase complex in the brain and excreted into CSF. For participants, who participated previously in study 54861911ALZ1005, the baseline CSF sample taken during that study may be used as baseline in this study. | Baseline and Month 6 |
| Percent Change From Baseline in Plasma ABeta 1-40 Levels and sAPP Fragments (sAPP-alpha, sAPP-beta), Total sAPP Levels | Plasma samples will be obtained for measuring levels of different ABeta fragments such as ABeta 1-37, ABeta 1-38, ABeta 1-40, ABeta 1-42. ABeta fragments of different length are produced by cleavage of the APP by beta-secretase (BACE) and the gamma-secretase complex in the different peripheral tissues, including white blood cells and can be measured in Plasma. | Baseline and Month 6 (Day 168) |
| Relationship Between Changes in CSF and Plasma ABeta Species and sAPP Fragments With Safety | ABeta species and sAPP fragments in plasma and CSF will be measured. Incidence of adverse events and their timing of onset will be examined with regard to these concentrations to assess potential relationships between safety and changes in the ABeta species and sAPP fragments. | Month 1 up to Month 6 |
| Maximum Plasma Concentration (Cmax) of JNJ-54861911 | The Cmax is the maximum observed plasma concentration. | Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168 |
| Time to Reach the Maximum Plasma or CSF concentration (Tmax) | The Tmax is the time to reach the maximum plasma or CSF concentration. | Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168 |
| Area Under the Plasma/CSF Concentration-time Curve From Time 0 to tau Hours Post Dosing (AUCtau) | AUCtau is the area under the plasma/CSF concentration-time curve from time 0 to tau hours post dosing. Time tau is the dosing interval. | Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168 |
| Hoboken |
| Belgium |
| Montpellier | France |
| Paris | France |
| Toulouse | France |
| Essen | Germany |
| Halle | Germany |
| Hamburg | Germany |
| Homburg | Germany |
| Lübeck | Germany |
| Tübingen | Germany |
| Ulm | Germany |
| Amsterdam | Netherlands |
| Barcelona | Spain |
| Madrid | Spain |
| Terrasa Barcelona N/A | Spain |
| Valencia | Spain |
| Mölndal | Sweden |
| Stockholm | Sweden |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000634126 | atabecestat |
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